Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways.Environ Toxicol Pharmacol. 2018 Mar; 58:212-219.ET
Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity.